Highlights d A given stimulus preferentially activates a single TrpA1 isoform in vivo d Polymodal nociception requires co-expression of TrpA1 isoforms in nociceptors d Each TrpA1 isoform has a unique expression profile d isoEXPRESS is a new and versatile framework targeting alternative splicing

Iron is an essential micronutrient for all forms of life; low levels of iron cause human disease, while too much iron is toxic. Low iron levels induce reactive oxygen species (ROS) by disruption of the heme and iron-sulfur cluster-dependent electron transport chain (ETC). To identify bacterial metabolites that affect development, we screened the Keio Escherichia coli collection and uncovered 244 gene deletion mutants that slow Caenorhabditis elegans development. Several of these genes encode members of the ETC cytochrome bo oxidase complex, as well as iron importers. Surprisingly, either iron or anti-oxidant supplementation reversed the developmental delay. This suggests that low bacterial iron results in high bacterial ROS and vice versa, which causes oxidative stress in C. elegans that subsequently impairs mitochondrial function and delays development. Our data indicate that the bacterial diets of C. elegans provide precisely tailored amounts of iron to support proper development.

Significance Functional plasticity of the nociceptive circuit is a remarkable feature and is of clinical relevance. As an example, nociceptors lower their threshold upon tissue injury, a process known as allodynia that would facilitate healing by guarding the injured areas. However, long-lasting hypersensitivity could lead to chronic pain, a debilitating disease not effectively treated. Therefore, it is crucial to dissect the mechanisms underlying basal nociception and nociceptive hypersensitivity. In both vertebrate and invertebrate species, conserved transient receptor potential (Trp) channels are the primary transducers of noxious stimuli. Here, we provide a precedent that in Drosophila larvae, heat sensing in the nociception and hypersensitivity states is mediated by distinct heat-sensitive neurons and TrpA1 alternative isoforms.

No abstract

Injured neurons exhibit cell type-specific axon regeneration, but the underlying mechanisms remain elusive. Two subtypes of Drosophila sensory neurons show distinct regenerative competence. Here, we show that axotomy induces long-lasting burst firing and Ca 2+ spikes specifically in the regenerative subtype. Genetic silencing of firing in the regenerative subtype inhibits regeneration. Optogenetic stimulation of the nonregenerative subtype reveals that activity patterns critically determine regeneration; burst firing triggers Ca 2+ spikes and suffices to induce regeneration, while tonic firing fails to induce Ca 2+ spikes and regeneration. We further show the L-type Ca 2+ channel, Dmca1D, regulates Ca 2+ spikes and regeneration. Intriguingly, the regenerative neuronal subtype expresses higher levels of Dmca1D, and overexpression of Dmca1D in the non-regenerative subtype facilitates regeneration. Our studies indicate that injury induces cell type-specific neuronal activities, which act through Ca 2+ spikes to govern regeneration, and suggest that precise control of neuronal activity patterns is an effective way to promote regeneration.